Highly accurate and effective deep neural networks in pathological diagnosis of prostate cancer.

PURPOSE: To established an AI system to make the pathological diagnosis of prostate cancer. METHODS: Prostate histopathological whole mount (WM) sections from patients underwent robot-assisted laparoscopic prostatectomy were prepared. All the prostate WM pathological sections were converted to digital image data and marked with different colors on the basis of the ISUP Gleason grade group. The image was then fed into a segmentation algorithm. We chose modified U-Net as our fundamental network architecture. RESULTS: 172 patients were involved in this study. 896 pieces of prostate WM pathological sections from 160 patients, in which 826 pieces of WM sections from 148 patients were assigned to the training set randomly. After image segmentation there were totally 2,138,895 patches, of which 1,646,535 patches were valid for training. The other WM section was arranged for testing. Based on the whole image testing, AI and pathologists presented the same answers among 21 of 22 pieces of sections. To evaluate the diagnostic results at the pixel level, we anticipated correct cancer or non-cancer diagnose from this AI system. The area under the ROC curve as 96.8%. The value of pixel accuracy of three methods (binary analysis, clinically oriented analysis and analysis for different ISUP Gleason grade) were 96.93%, 95.43% and 93.88%, respectively. The value of frequency weighted IoU were 94.32%, 92.13% and 90.21%, respectively. CONCLUSIONS: This AI system is able to assist pathologists to make a final diagnosis, indicating the great potential and a wide-range of applications of AI in the medical field.

Androgen deprivation therapy plus abiraterone or docetaxel as neoadjuvant therapy for very-high-risk prostate cancer: a pooled analysis of two phase II trials.

Objective: The study aimed to compare the efficacy and safety of androgen deprivation therapy (ADT) with abiraterone or docetaxel versus ADT alone as neoadjuvant therapy in patients with very-high-risk localized prostate cancer. Methods: This was a pooled analysis of two single-center, randomized, controlled, phase II clinical trials (ClinicalTrials.gov: NCT04356430 and NCT04869371) conducted from December 2018 to March 2021. Eligible participants were randomly assigned to the intervention (ADT plus abiraterone or docetaxel) and control (ADT alone) groups at a 2:1 ratio. Efficacy was evaluated by pathological complete response (pCR), minimal residual disease (MRD), and 3-year biochemical progression-free survival (bPFS). Safety was also analyzed. Results: The study included 42 participants in the ADT group, 47 in the ADT plus docetaxel group, and 48 in the ADT plus abiraterone group. A total of 132 (96.4%) participants had very-high-risk prostate cancer, and 108 (78.8%) had locally advanced disease. The ADT plus docetaxel group (28%) and ADT plus abiraterone group (31%) had higher rates of pCR or MRD (p = 0.001 and p < 0.001) compared with the ADT group (2%). The 3-year bPFS was 41.9% (95% CI: 26.6-57.2), 51.1% (95% CI: 36.8-65.4), and 61.2% (95% CI: 45.5-76.9), respectively. Significant difference was found among groups in terms of bPFS (p = 0.037). Conclusion: Compared with ADT alone, neoadjuvant therapy with ADT plus docetaxel or abiraterone could achieve better pathological outcomes (pCR or MRD) for very-high-risk localized prostate cancer. The ADT plus abiraterone group showed longer bPFS than ADT alone. The combination regimens were tolerable.

A retrospective study to evaluate the effect of preoperative hormonal therapy on continence recovery.

Objective: To evaluate whether different preoperative hormonal therapy options affect postoperative continence and to identify risk/protective factors for continence recovery. Methods: This is a retrospective analysis of several clinical trials (NCT04356430, NCT04869371, NCT04992026 and NCT05406999). Data from patients treated with hormonal therapy followed by RARP were collected and analyzed. Continence was defined as 0 pad/day or one safety pad. Results: The study included 230 patients with adequate information. The median time to continence recovery is 8 weeks. A total of 216 (93.9%) participants recovered to urinary continence within 12 months after surgery. 21 (9.1%) participants achieved immediate continence. 69, 85, 27 and 14 participants restored continence at 1 month, 1-3 month, 3-6 month, 6-12 month, accounting for 30.0%, 40.0%, 11.7% and 6.1% accordingly. No difference in continence recovery was found among different preoperative hormonal treatment options (p=0.821). Cox regression showed that membranous urethral length (MUL) was the only independent factor influencing urinary continence recovery either in the univariate analysis (OR=1.13, 95%CI: 1.04-1.22, p=0.002) or in the multivariate analysis (OR=1.12, 95%CI: 1.04-1.20, p=0.002). Different preoperative treatment options were not associated with urinary recovery. More advanced preoperative T stage (OR=0.46, 95%CI: 0.24-0.85, p=0.014) delayed the recovery of immediate continence. MUL was associated with continence restoring at 1 month (OR=1.20, 95%CI: 1.03-1.39, p=0.017), 3 month (OR=1.27, 95%CI: 1.07-1.51, p=0.006), 6 month (OR=1.34, 95%CI: 1.07-1.67, p=0.011) and 12 month (OR=1.36, 95%CI: 1.01-1.84, p=0.044). Conclusion: There is no difference in postoperative continence recovery among ADT, ADT+Docetaxel and ADT+Abiraterone preoperative treatment options. More advanced T stage indicated poor immediate continence recovery. Longer membranous urethral length was a promotional factor for both short-time and long-time continence recovery.

Correlation between the platelet-to-lymphocyte ratio and diabetic foot ulcer in patients with type 2 diabetes mellitus.

OBJECTIVE: To investigate the correlation between the platelet-to-lymphocyte ratio (PLR) and diabetic foot ulcer (DFU) in patients with type 2 diabetes mellitus (T2DM). METHOD: From January 2018 to August 2019, 206 patients with T2DM admitted to the Central Hospital of Wuhan, China, were enrolled in this study, including 104 patients with DFU (DFU group) and 102 patients without DFU (T2DM group). During the same period, 90 healthy subjects were randomly screened as normal controls (NC group). The correlation between PLR and DFU in patients with T2DM was explored by comparing the PLR of the subjects in the three groups. RESULTS: The PLRs of the DFU and T2DM groups were higher than that of the NC group, whereas the PLR of the DFU group was higher than that of the T2DM group (p < 0.05). PLR was positively correlated with the Wagner DFU grade (p < 0.001). Based on logistic regression analysis, PLR was found to be an independent risk factor for DFU (OR =1.029, 95% CI: 1.019 ~ 1.039, p < 0.001). The receiver operating characteristic curve analysis of the PLR showed that the area under the curve of the PLR for predicting diabetic foot ulcer was 0.776 (p < 0.001), and the analysis determined that the optimal critical value of the PLR for predicting DFU was 147.6. CONCLUSION: The PLR is significantly elevated in patients with DFU and positively correlated with the Wagner DFU grade, which might be a valuable marker for early diagnosis and assessment of severity of DFU.

A cohort study of 676 patients indicates D-dimer is a critical risk factor for the mortality of COVID-19.

Coronavirus Disease 2019 (COVID-19) has recently become a public emergency and a worldwide pandemic. However, the information on the risk factors associated with the mortality of COVID-19 and of their prognostic potential is limited. In this retrospective study, the clinical characteristics, treatment and outcome data were collected and analyzed from 676 COVID-19 patients stratified into 140 non-survivors and 536 survivors. We found that the levels of Dimerized plasmin fragment D (D-dimer), C-reactive protein (CRP), lactate dehydrogenase (LDH), procalcitonin (PCT) were significantly higher in non-survivals on admission (non-survivors vs. survivors: D-Dimer ≥ 0.5 mg/L, 83.2% vs. 44.9%, P<0.01; CRP ≥10 mg/L, 50.4% vs. 6.0%, P<0.01; LDH ≥ 250 U/L, 73.8% vs. 20.1%, P<0.01; PCT ≥ 0.5 ng/ml, 27.7% vs. 1.8%, P<0.01). Moreover, dynamic tracking showed D-dimer kept increasing in non-survivors, while CRP, LDH and PCT remained relatively stable after admission. D-dimer has the highest C-index to predict in-hospital mortality, and patients with D-dimer levels ≥0.5 mg/L had a higher incidence of mortality (Hazard Ratio: 4.39, P<0.01). Our study suggested D-dimer could be a potent marker to predict the mortality of COVID-19, which may be helpful for the management of patients.

High aspartate aminotransferase to alanine aminotransferase ratio on admission as risk factor for poor prognosis in COVID-19 patients.

This study aimed to analyze aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio in COVID-19 patients. After exclusion, 567 inpatients were included in this study and separated into two groups according to their AST/ALT ratio on admission. Death was regarded as poor prognosis in this study. Of 567 patients, 200 (35.3%) had AST/ALT ≥ 1.38. Of the 200 patients, older age (median age 60 years), myalgia (64 [32%] cases), fatigue (91 [45.5%] cases), some comorbidities and outcomes were significantly different from patients with AST/ALT < 1.38. They also had worse chest computed tomography (CT) findings, laboratory results and severity scores. Levels of platelet count (OR 0.995, 95% CI [0.992-0.998]) and hemoglobin (OR 0.984, 95% CI [0.972-0.995]) were independently associated with AST/ALT ≥ 1.38 on admission. Furthermore, a high AST/ALT ratio on admission was an independent risk factor for poor prognosis (OR 99.9, 95% CI [2.1-4280.5]). In subsequent monitoring, both survivors and non-survivors showed decreased AST/ALT ratio during hospitalization. In conclusion, high AST/ALT ratio might be the indication of worse status and outcomes in COVID-19 patients.

Autologous Bone Marrow Mononuclear Cell Transplantation Therapy Improved Symptoms in Patients with Refractory Diabetic Sensorimotor Polyneuropathy via the Mechanisms of Paracrine and Immunomodulation: A Controlled Study.

TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-TRC-12002570.URL: http://www.chictr.org.cn/showproj.aspx?proj=6981.

Long non-coding RNA PVT1, a novel biomarker for chronic obstructive pulmonary disease progression surveillance and acute exacerbation prediction potentially through interaction with microRNA-146a.

OBJECTIVE: This study aimed to investigate the abilities of long non-coding RNA PVT1 (lnc-PVT1) and microRNA-146a (miR-146a) in predicting chronic obstructive pulmonary disease (COPD) susceptibility and acute exacerbation risk, moreover, to explore the association of lnc-PVT1 with disease severity, inflammation, and miR-146a in patients with COPD. METHODS: A total of 80 acute exacerbation of COPD (AECOPD) patients, 80 stable COPD patients, and 80 healthy controls (HCs) were consecutively recruited. Peripheral blood samples of all participants were collected to isolate peripheral blood mononuclear cells (PBMCs), and serum: PBMCs were used to detect lnc-PVT1 and miR-146a by RT-qPCR; serum was used to detect inflammatory cytokines by ELISA. Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage of COPD was assessed. RESULTS: Lnc-PVT1 expression was highest in AECOPD patients, followed by stable COPD patients and HCs. Receiver operating characteristic curves disclosed that lnc-PVT1 distinguished AECOPD patients and stable COPD patients from HCs, also distinguished AECOPD patients from stable COPD patients. In AECOPD patients and stable COPD patients, lnc-PVT1 expression positively correlated with GOLD stage and levels of TNF-α, IL-6, IL-8, and IL-17. Moreover, lnc-PVT1 was negatively correlated with miR-146a. For miR-146a, its expression was lowest in AECOPD patients, followed by stable COPD patients and HCs, and it predicted reduced COPD susceptibility and decreased acute exacerbation risk; meanwhile, it negatively correlated with GOLD stage and inflammatory cytokine levels in AECOPD patients and stable COPD patients. CONCLUSION: Lnc-PVT1 assists the disease management and acute exacerbation risk monitoring of COPD via interaction with miR-146a.

Efficacy of autologous bone marrow mononuclear cell transplantation therapy in patients with refractory diabetic peripheral neuropathy.

BACKGROUND: Owing to the multifactorial nature of the pathogenesis of diabetic peripheral neuropathy (DPN), conventional drug therapies have not been effective. The application of stem cells transplantation may be useful for the treatment of DPN. This study was designed to assess the safety and therapeutic effects of autologous bone marrow mononuclear cells (BMMNCs) transplantation on the treatment of refractory DPN. METHODS: One hundred and sixty-eight patients with refractory DPN were recruited and enrolled in the study. They received intramuscular injection of BMMNCs and followed at 1, 3, 6, 12, 18, 24, and 36 months after the transplantation. Clinical data, Toronto Clinical Scoring System (TCSS), and nerve conduction studies (NCSs) were compared before and after the transplantation. RESULTS: The signs and symptoms of neuropathy were significantly improved after BMMNCs transplantation. The values of the TCSS scores at 1 month (9.68 ±â€Š2.49 vs. 12.55 ±â€Š2.19, P < 0.001) and 3 months (8.47 ±â€Š2.39 vs. 12.55 ±â€Š2.19, P < 0.001) after the treatment reduced significantly compared with the baseline value. This decrement remained persistent until the end of the study. The conduction velocity and action potential and sensory nerves were significantly improved after transplantation (3 and 12 months after the treatment vs. the baseline: motor nerve conduction velocity, 40.24 ±â€Š2.80 and 41.00 ±â€Š2.22 m/s vs. 38.21 ±â€Š2.28 m/s, P < 0.001; sensory nerve conduction velocity, 36.96 ±â€Š2.26 and 39.15 ±â€Š2.61 m/s vs. 40.41 ±â€Š2.22 m/s, P < 0.001; compound muscle action potential, 4.67 ±â€Š1.05 and 5.50 ±â€Š1.20 µV vs. 5.68 ±â€Š1.08 µV, P < 0.001; sensory nerve action potential, 4.29 ±â€Š0.99 and 5.14 ±â€Š1.26 µV vs. 5.41 ±â€Š1.14 µV, P < 0.001). No adverse event associated with the treatment was observed during the follow-up period. CONCLUSIONS: Autologous transplantation of BMMNCs may be an effective and promising therapeutic strategy for the treatment of refractory DPN.